rs9535307

Variant names:

• chr13-49717706-A-C
• rs9535307
• NM_002267.4:c.771+2069T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-49717706-A-C
• chr13-49717706-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002267.4(KPNA3):​c.771+2069T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,116 control chromosomes in the GnomAD database, including 54,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (54575 hom., cov: 32)
• Consequence: KPNA3 NM_002267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 4 publications found

Genes affected

KPNA3 (HGNC:6396): (karyopherin subunit alpha 3) The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import. [provided by RefSeq, Jan 2009]

KPNA3 Gene-Disease associations (from GenCC):

• spastic paraplegia 88, autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002267.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA3	NM_002267.4	MANE Select	c.771+2069T>G		intron	N/A	NP_002258.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA3	ENST00000261667.8	TSL:1 MANE Select	c.771+2069T>G		intron	N/A	ENSP00000261667.3

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128463 AN: 151998 Hom.: 54526 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.830

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.845 AC: 128570 AN: 152116 Hom.: 54575 Cov.: 32 AF XY: 0.847 AC XY: 62974 AN XY: 74342

African (AFR) AF: 0.773 AC: 32048 AN: 41450

American (AMR) AF: 0.874 AC: 13368 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2742 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5176 AN: 5186

South Asian (SAS) AF: 0.924 AC: 4460 AN: 4828

European-Finnish (FIN) AF: 0.846 AC: 8945 AN: 10576

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58933 AN: 67992

Other (OTH) AF: 0.832 AC: 1760 AN: 2116

Alfa AF: 0.842 Hom.: 34283

Bravo AF: 0.846

Asia WGS AF: 0.946 AC: 3287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.78
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9535307; hg19: chr13-50291842;